Pediatrics 2018 Apr;141(Suppl 5):S445-S450

Departments of Pathology and Immunology and

The porphyrias are a group of rare metabolic disorders that result from defects in heme biosynthesis. Erythropoietic protoporphyria (EPP) is the most common inherited porphyria in children and is diagnosed in most individuals after the onset of cutaneous manifestations. Hepatobiliary disease affects the minority of individuals with EPP and usually manifests in patients with an established diagnosis of EPP. Read More

Rambam Maimonides Med J 2018 Mar 15:1-12. Epub 2018 Mar 15.

Porphyria Center, Rabin Medical Center, Beilinson Hospital, Petach Tikva, Israel.

The porphyrias are a group of rare metabolic disorders, inherited or acquired, along the heme biosynthetic pathway, which could manifest with neurovisceral and/or cutaneous symptoms, depending on the defective enzyme. Neurovisceral porphyrias are characterized by acute attacks, in which excessive heme production is induced following exposure to a trigger. An acute attack usually presents with severe abdominal pain, vomiting, and tachycardia. Read More

Br J Dermatol 2018 Jan 17. Epub 2018 Jan 17.

Porphyria Center, Center for Lysosomal and Metabolic Diseases, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands.

J Dermatol 2018 Feb 20;45(2):145-149. Epub 2017 Dec 20.

Department of Dermatology, Kindai University Faculty of Medicine, Osaka, Japan.

Erythropoietic protoporphyria is a genetic disease characterized by sensitivity to sunlight caused by the accumulation of protoporphyrin IX. Photoprotection against ultraviolet A and visible light is necessary for erythropoietic porphyria patients because the absorption spectrum of protoporphyrin IX lies in both ultraviolet A and visible light region. We developed a novel index, in vitro porphyrin protection factor, based on the protoporphyrin IX absorbance spectrum. Read More

Pain 2017 Nov 25. Epub 2017 Nov 25.

aInstitute of Academic Anaesthesia, Division of Neuroscience, Ninewells Hospital, University of Dundee, Dundee, United KingdombPhotobiology Unit, Ninewells Hospital, University of Dundee, Dundee, United Kingdom.

Phototoxicity-induced pain is a major clinical problem triggered by light acting on photosensitising drugs or endogenous porphyrins, notably protoporphyrin IX (PpIX), an intermediary in heme biosynthesis. Protoporphyrin IX accumulates in individuals with erythropoietic protoporphyria and is elevated during photodynamic therapy subsequent to application of 5-aminolevulinic acid (ALA). Pain occurs during irradiation of PpIX and responds poorly to conventional analgesics. Read More

F1000Res 2017 30;6:1906. Epub 2017 Oct 30.

Scottish Cutaneous Porphyria Service, Scottish Photodiagnostic Unit, Department of Dermatology, Ninewells Hospital and Medical School, Dundee, DD1 9SY, UK.

This is an overview of the cutaneous porphyrias. It is a narrative review based on the published literature and my personal experience; it is not based on a formal systematic search of the literature. The cutaneous porphyrias are a diverse group of conditions due to inherited or acquired enzyme defects in the porphyrin-haem biosynthetic pathway. Read More

Am J Transplant 2018 Mar 9;18(3):745-749. Epub 2017 Dec 9.

Department of Medicine, Division of Gastroenterology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.

Erythropoietic protoporphyria (EPP) is a rare inherited disorder of the heme biosynthesis pathway resulting in the accumulation of protoporphyrins in the blood, erythrocytes, and other tissues. Because of a gene mutation in the FECH gene, ferrochelatase, the enzyme involved in the final step of heme synthesis, is deficient in these patients. Although the major symptom of this disorder is photosensitivity, rarely, it can cause progressive liver disease requiring liver transplantation (LT). Read More

Acta Derm Venereol 2018 Feb;98(2):275-277

Division of Dermatology, Department of Internal Medicine, Kobe University Graduate School of Medicine , Kobe University Graduate School of Medicine, 6500017 5-2, Kusunoki-cho7, Chuo-ku, Kobe-shi, Hyougo, Kobe, Japan.

Zhonghua Bing Li Xue Za Zhi 2017 Oct;46(10):704-707

Department of Pathology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Science, Beijing 100730, China.

To investigate the clinicopathologic features of the erythropoietic protoporphyria (EPP) with liver involvement. The clinical findings and hepatic biopsy of 3 cases of EPP diagnosed between July, 2011 to August, 2014 with liver involvement were reviewed, with relevant literature review. All patients presented with persistent and refractory abdominal pain, with obvious jaundice and deranged liver function. Read More

Proc (Bayl Univ Med Cent) 2017 Oct;30(4):450-451

Division of Hematopathology, Department of Pathology (Krause, Baugh) and the Department of Hematology/Oncology (Swink, Burch), Baylor University Medical Center at Dallas and Baylor Sammons Cancer Center, Dallas, Texas.

A 56-year-old Texas rancher with a prior diagnosis of acquired erythropoietic protoporphyria secondary to an underlying myelodysplastic disorder developed an uncommon tumor, blastic plasmacytoid dendritic cell neoplasm (BPDCN). During his initial disease, analysis revealed a mutation, which is the most common mutation associated with BPDCN. This article discusses this unusual hematopoietic neoplasm, the possible evolution from erythropoietic protoporphyria, and the underlying myelodysplastic process. Read More

J Cutan Med Surg 2017 May/Jun;21(3):270-271

Proc Natl Acad Sci U S A 2017 Sep 5;114(38):E8045-E8052. Epub 2017 Sep 5.

Division of Hematology, Brigham & Women's Hospital, Harvard Medical School, Boston, MA 02115;

Loss-of-function mutations in genes for heme biosynthetic enzymes can give rise to congenital porphyrias, eight forms of which have been described. The genetic penetrance of the porphyrias is clinically variable, underscoring the role of additional causative, contributing, and modifier genes. We previously discovered that the mitochondrial AAA+ unfoldase ClpX promotes heme biosynthesis by activation of δ-aminolevulinate synthase (ALAS), which catalyzes the first step of heme synthesis. Read More

N Engl J Med 2017 Aug;377(9):862-872

From the Department of Medicine, Division of Gastroenterology and Porphyria Center, University of California, San Francisco, San Francisco (D.M.B.); the Departments of Preventive Medicine and Community Health and Internal Medicine, Division of Gastroenterology and Hepatology, University of Texas Medical Branch, Galveston (K.E.A.); and the Department of Gastroenterology, Wake Forest School of Medicine, Winston-Salem, NC (H.L.B.).

Br J Dermatol 2017 Dec 22;177(6):1693-1698. Epub 2017 Nov 22.

Department of Internal Medicine, Porphyria Centre, Centre for Lysosomal and Metabolic Diseases, Erasmus MC, PO Box 2040, 3000, CA Rotterdam, the Netherlands.

Background: Erythropoietic protoporphyria (EPP) is a rare metabolic disease with painful photosensitivity due to protoporphyrin IX accumulation.

Objectives: To evaluate bone mineral density (BMD) and known osteoporosis risk factors in patients with EPP.

Methods: Patients with EPP attending the Erasmus MC outpatient clinic who had undergone BMD measurements were included. Read More

Br J Dermatol 2018 Feb 20;178(2):567-568. Epub 2018 Jan 20.

Photodermatology Department, St John's Institute of Dermatology, Guy's Hospital, London, SE1 9RH, U.K.

Clin J Gastroenterol 2017 Oct 4;10(5):452-458. Epub 2017 Jul 4.

Department of Internal Medicine, Division of Gastroenterology, Shinshu University School of Medicine, Matsumoto, Japan.

A 21-year-old Japanese man was admitted to our hospital because of severe abdominal pain and jaundice. He had been suffering from abdominal pain attacks and liver dysfunction since 18 years of age. Liver histology showed amorphous brown deposits in the sinusoidal space and significant periportal fibrosis without apparent hepatitis. Read More

JAMA Dermatol 2017 Aug;153(8):789-796

Department of Genetics and Genomic Sciences, Mount Sinai School of Medicine, New York, New York.

Importance: Autosomal recessive erythropoietic protoporphyria (EPP) and X-linked protoporphyria (XLP) are rare photodermatoses presenting with variable degrees of painful phototoxicity that markedly affects quality of life. The clinical variability, determinants of severity, and genotype/phenotype correlations of these diseases are not well characterized.

Objective: To describe the baseline clinical characteristics, genotypes, and determinants of disease severity in a large patient cohort with EPP or XLP. Read More

JAAD Case Rep 2017 May 13;3(3):169-171. Epub 2017 Apr 13.

Department of Dermatology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan.

J Inherit Metab Dis 2017 May 9;40(3):433-441. Epub 2017 Feb 9.

Porphyria Centre San Gallicano Dermatological Institute IRCCS, Rome, Italy.

Patients with erythropoietic protoporphyria (EPP) have reduced activity of the enzyme ferrochelatase that catalyzes the insertion of iron into protoporphyrin IX (PPIX) to form heme. As the result of ferrochelatase deficiency, PPIX accumulates and causes severe photosensitivity. Among different patients, the concentration of PPIX varies considerably. Read More

Curr Opin Hematol 2017 May;24(3):198-207

aINSERM U1149 CNRS ERL 8252, Centre de Recherche sur l'inflammation, Université Paris Diderot, site Bichat, Sorbonne Paris Cité bLaboratory of excellence, GR-Ex, Paris cAP-HP, Centre Français des Porphyries, Hôpital Louis Mourier, Colombes dAP-HP, Hôpital Beaujon, Service de Biochimie Clinique, Clichy, France.

Purpose Of Review: Many studies over the past decade have together identified new genes including modifier genes and new regulation and pathophysiological mechanisms in inherited inborn diseases of the heme biosynthetic pathway. A new porphyria has been characterized: X-linked protoporphyria and the perspective to have innovative treatment at very short-term became a reality. We will summarize how recent data on both ALAS1 and ALAS2 have informed our understanding of disease pathogenesis with an emphasis on how this information may contribute to new therapeutic strategies. Read More

Dis Model Mech 2017 03 12;10(3):225-233. Epub 2017 Jan 12.

Institute of Laboratory Medicine, Municipal Hospital Triemli, Zürich 8063, Switzerland

Erythropoietic protoporphyria (EPP) is caused by deficiency of ferrochelatase (FECH), which incorporates iron into protoporphyrin IX (PPIX) to form heme. Excitation of accumulated PPIX by light generates oxygen radicals that evoke excessive pain and, after longer light exposure, cause ulcerations in exposed skin areas of individuals with EPP. Moreover, ∼5% of the patients develop a liver dysfunction as a result of PPIX accumulation. Read More

Clin Genet 2017 Nov 2;92(5):495-502. Epub 2017 Aug 2.

Department of Biochemistry and Molecular Genetics, American University of Beirut, Beirut, Lebanon.

Erythropoietic protoporphyria (EPP) is a rare cutaneous and systemic disease caused by mutations in the ferrochelatase gene (FECH). The molecular underpinnings of EPP in Middle Eastern populations and relative to other ethnic groups secondary to increased consanguinity are unknown. To understand the molecular pathogenesis of Middle Eastern EPP, we surveyed clinicopathological and molecular features in 6 large consanguineous families from Lebanon and Syria presenting with cutaneous and systemic features consistent with EPP. Read More

Clin Pharmacokinet 2017 Aug;56(8):815-823

Stadtspital Triemli, Institute of Laboratory Medicine, Zurich, Switzerland.

Afamelanotide, the first α-melanocyte-stimulating hormone (MSH) analogue, synthesized in 1980, was broadly investigated in all aspects of pigmentation because its activity and stability were higher than the natural hormone. Afamelanotide binds to the melanocortin-1 receptor (MC1R), and MC1R signaling increases melanin synthesis, induces antioxidant activities, enhances DNA repair processes and modulates inflammation. The loss-of-function variants of the MC1R present in fair-skinned Caucasians are less effectively activated by the natural hormone. Read More

Int J Dermatol 2017 Mar 4;56(3):272-276. Epub 2017 Jan 4.

Department of Dermatology, National Skin Center, Singapore.

Background: Erythropoietic protoporphyria (EPP) is a rare inherited disorder of heme biosynthesis caused by decreased activity of the enzyme ferrochelatase (FECH ). The frequency of the hypomorphic c.333-48C allele in a population directly contributes to the prevalence of EPP in the same population. Read More

J Dermatol 2017 Jun 27;44(6):651-655. Epub 2016 Dec 27.

Department of Dermatology, Tohoku University Graduate School of Medicine, Sendai, Japan.

We report the case of a 42-year-old man with a 5-year history of myelodysplastic syndrome and photosensitivity who had developed painful erythema and blisters on sun-exposed sites. Histological examination of a mildly lichenified lesion on the dorsal finger revealed extensive deposits of a hyaline-like, periodic acid-Schiff-positive material around superficial dermal blood vessels. Laboratory tests showed elevated erythrocyte protoporphyrin and normal urinary porphyrins, suggesting a diagnosis of erythropoietic protoporphyria. Read More

Appl Clin Genet 2016 12;9:179-189. Epub 2016 Dec 12.

Department of Internal Medicine, Section on Gastroenterology.

Erythropoietic protoporphyria (EPP) and the phenotypically similar disease X-linked protoporphyria (XLPP) are inherited cutaneous porphyrias characterized clinically by acute non-blistering photosensitivity, intolerance to sunlight, and significantly reduced quality of life. They are due to marked overproduction of protoporphyrin (PP) chiefly by erythroblasts and reticulocytes. In EPP, the underlying genetic defect is in the ferrochelatase gene, which encodes the final enzyme in the heme synthetic pathway. Read More

Br J Dermatol 2016 Dec;175(6):1144-1145

Scottish Cutaneous Porphyria Service, Photobiology Unit, Level 8, Ninewells Hospital, Dundee, DD1 9SY, U.K.

Br J Dermatol 2017 09 3;177(3):e38-e40. Epub 2017 Jul 3.

Department of Dermatology D92, Bispebjerg Hospital, University of Copenhagen, Bispebjerg Bakke 23, DK-2400, Copenhagen, Denmark.

Cureus 2016 Oct 24;8(10):e841. Epub 2016 Oct 24.

Radiation Oncology, University of Utah Huntsman Cancer Hospital.

The standard of care for localized hepatocellular carcinoma (HCC) is surgical resection. For patients who decline or who are unfit for surgery, stereotactic body radiotherapy (SBRT) is emerging as a viable treatment approach. We present a case of a 77-year-old female in whom an early stage HCC was incidentally discovered. Read More

J Cutan Med Surg 2017 May/Jun;21(3):258-260. Epub 2016 Nov 12.

2 Department of Internal Medicine, College of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada.

Background: Basal cell carcinoma (BCC) is the most common nonmelanoma skin cancer. There is a clear association between BCC development and ultraviolet (UV) radiation. Erythropoietic protoporphyria (EPP) is an inherited porphyria disorder that is a result of protoporphyrin accumulation, typically manifesting with phototoxicity. Read More

Br J Dermatol 2016 Dec 17;175(6):1284-1289. Epub 2016 Oct 17.

Department of Dermatology, Bispebjerg Hospital, University of Copenhagen, Copenhagen, Denmark.

Background: Erythropoietic protoporphyria (EPP) is a rare genetic disease that causes severe sensitivity to visible light as a result of protoporphyrin IX (PpIX) accumulation in the skin.

Objectives: To establish a noninvasive method to measure PpIX in the skin of patients with EPP and to investigate how skin PpIX relates to erythrocyte PpIX and photosensitivity.

Methods: Skin PpIX was measured in 25 patients with EPP by calculating the difference in PpIX fluorescence before and after complete photobleaching of PpIX using controlled illumination. Read More

J Zhejiang Univ Sci B 2016 Oct.;17(10):813-820

Department of Hematology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China.

Erythropoietic protoporphyria (EPP), an autosomal dominant disease, is caused by partial deficiency of ferrochelatase (FECH), which catalyzes the terminal step of heme biosynthesis because of loss-of-function mutations in the FECH gene. To date, only a few cases have been described in Asia. In this study, we describe the clinical features of two Chinese patients with EPP, with diagnosis confirmed by the increase of free protoporphyrin in erythrocytes, detection of plasma fluorescence peak at 630-634 nm, and analysis of FECH gene mutations. Read More

JAMA Dermatol 2016 Nov;152(11):1258-1261

Department of Dermatology, Stanford University, Stanford, California.

Importance: Erythropoietic protoporphyria (EPP) is a rare hereditary disease of heme biosynthesis that manifests as severe photosensitivity and hepatotoxicity. There have been no effective treatments to date. Cimetidine has been shown to inhibit heme biosynthesis and results in symptomatic improvement in patients with acute intermittent porphyria (AIP) and porphyria cutanea tarda (PCT). Read More

Proc (Bayl Univ Med Cent) 2016 Jul;29(3):311-2

Department of Pathology, University of South Carolina, Charleston (Lindsey); and the Departments of Hematology/Oncology (Burch) and Pathology (Krause), Baylor University Medical Center at Dallas and Baylor Sammons Cancer Center, Dallas, Texas.

A 53-year-old Texas rancher developed a blistering skin rash that was sensitive to exposure to sunlight. He was referred to hematology with a presumptive diagnosis of porphyria. His peripheral blood counts were within normal limits, and a bone marrow examination revealed erythroid dyspoiesis and ringed sideroblasts. Read More

Am J Hum Genet 2016 Jul 23;99(1):8-21. Epub 2016 Jun 23.

Department of Medicine, Université de Montréal, Montréal, QC H3T 1J4, Canada; Montreal Heart Institute, Montréal, QC H1T 1C8, Canada. Electronic address:

Red blood cell (RBC) traits are important heritable clinical biomarkers and modifiers of disease severity. To identify coding genetic variants associated with these traits, we conducted meta-analyses of seven RBC phenotypes in 130,273 multi-ethnic individuals from studies genotyped on an exome array. After conditional analyses and replication in 27,480 independent individuals, we identified 16 new RBC variants. Read More

Acta Derm Venereol 2016 Nov;96(7):868-872

Department of Clinical Biochemistry and Pharmacology, Odense University Hospital, 5000 Odense C, Denmark.

Porphyrias are rare diseases caused by altered haem synthesis leading to the accumulation of different haem intermediates. Neurovisceral attacks may occur in acute porphyrias, while photosensitivity is the presenting symptom in cutaneous porphyrias. We present here an overview of symptoms and a flowchart for the diagnosis of cutaneous porphyrias, with recommendations for monitoring and an update of treatment options. Read More

JAMA Dermatol 2016 08;152(8):937-8

Harvard Medical School, Boston, Massachusetts2Dermatology Program, Boston Children's Hospital, Boston, Massachusetts.

Hautarzt 2016 Jun;67(6):479-82

Klinik für Dermatologie, Venerologie und Allergologie, Universitätsklinikum Frankfurt, Theodor-Stern-Kai 7, 60590, Frankfurt am Main, Deutschland.

Erythropoietic protoporphyria results in highly increased photosensitivity of the skin. Solar irradiation causes sunburn-like symptoms with erythema, edema and wheals. We report the case of a 60-year-old man suffering from erythropoietic protoporphyria since his childhood who additionally developed chronic cutaneous lichenoid papules in sun-exposed skin areas. Read More

Br J Dermatol 2016 Oct 13;175(4):768-75. Epub 2016 Jul 13.

Department of Dermatology, Centre Hospitalier Universitaire (CHU) Hôtel-Dieu, 1, place Alexis-Ricordeau, 44093, Nantes Cedex 1, France.

Background: Erythropoietic protoporphyria (EPP) is a rare metabolic disorder, characterized by photosensitivity, caused by errors of the haem biosynthetic pathway. Avoidance of sun exposure is recommended; however, some patients suggested a paradoxical improvement of symptoms when they move to sunny areas.

Objectives: In a national French study, we sought to investigate the influence of sun exposure on EPP symptoms. Read More

Am J Clin Dermatol 2016 Apr;17(2):179-85

Springer, Private Bag 65901, Mairangi Bay 0754, Auckland, New Zealand.

Afamelanotide (SCENESSE(®)) is a synthetic α-melanocyte stimulating hormone analogue and first-in-class melanocortin-1 receptor agonist that is approved in the EU for the prevention of phototoxicity in adults with erythropoietic protoporphyria (EPP). It is administered subcutaneously as a biodegradable, controlled-release implant containing 16 mg of afamelanotide. This article reviews the clinical efficacy and tolerability of afamelanotide in EPP and summarizes its pharmacological properties. Read More

FASEB J 2016 05 2;30(5):1798-810. Epub 2016 Feb 2.

Department of Molecular and Integrative Physiology, Department of Internal Medicine, and Veterans Affairs Ann Arbor Healthcare System, Ann Arbor, Michigan, USA

Protoporphyria is a metabolic disease that causes excess production of protoporphyrin IX (PP-IX), the final biosynthetic precursor to heme. Hepatic PP-IX accumulation may lead to end-stage liver disease. We tested the hypothesis that systemic administration of porphyrin precursors to zebrafish larvae results in protoporphyrin accumulation and a reproducible nongenetic porphyria model. Read More

Folia Biol (Praha) 2015 ;61(6):227-32

Department of Paediatrics and Adolescent Medicine, First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague, Czech Republic.

Erythropoietic protoporphyria (EPP), a chronic erythropoietic porphyria, is characterized by excess accumulation of protoporphyrin, particularly in erythroid cells. EPP inheritance is complex, almost always associated with two molecular defects. In most EPP patients, clinical expression requires coinheritance of a private ferrochelatase (FECH) mutation trans- to a hypomorphic FECH*IVS3-48C allele. Read More

Hautarzt 2016 Mar;67(3):211-5

Hautklinik und Europäisches Porphyriezentrum, Universitätsklinikum der Heinrich-Heine-Universität Düsseldorf, 40225, Düsseldorf, Moorenstr. 5, Deutschland.

Background: Erythropoietic protoporphyria, the second most common type of the cutaneous porphyrias, is due to an enzymatic deficiency of ferrochelatase, the last enzyme in heme biosynthesis. The enzyme defect leads to an accumulation of protoporphyrin IX in erythrocytes and an elevated excretion of this metabolite in the feces.

Clinical Presentation: Usually, disease onset is in early infancy, characterized by increased photosensitivity. Read More

J Dtsch Dermatol Ges 2015 Dec;13(12):1250-3

Department of Dermatology, University Medical Center Jena, Jena, Germany.

Solar urticaria is a rare IgE-mediated and chromophore-dependent photodermatosis. In some cases, these chromophores, designated as "serum factor", may be detected in serum or plasma. To date, the exact pathogenesis of solar urticaria has, however, not been elucidated. Read More

Vet Rec 2015 Oct;177(17):432-5

Clin Chem 2015 Dec 19;61(12):1453-6. Epub 2015 Oct 19.

University of Texas Medical Branch, Galveston, TX;

Background: Laboratory diagnosis of erythropoietic protoporphyria (EPP) requires a marked increase in total erythrocyte protoporphyrin (300-5000 μg/dL erythrocytes, reference interval <80 μg/dL) and a predominance (85%-100%) of metal-free protoporphyrin [normal, mostly zinc protoporphyrin (reference intervals for the zinc protoporphyrin proportion have not been established)]; plasma porphyrins are not always increased. X-linked protoporphyria (XLP) causes a similar increase in total erythrocyte protoporphyrin with a lower fraction of metal-free protoporphyrin (50%-85% of the total).

Content: In studying more than 180 patients with EPP and XLP, the Porphyrias Consortium found that erythrocyte protoporphyrin concentrations for some patients were much higher (4. Read More

Hepatology 2016 07 30;64(1):305. Epub 2015 Oct 30.

Center for Pharmacogenetics, Department of Pharmaceutical Sciences School of Pharmacy, University of Pittsburgh, Pittsburgh, PA.

J Dermatol 2016 Apr 21;43(4):414-8. Epub 2015 Sep 21.

Department of Dermatology, Osaka Medical College, Osaka, Japan.

A 12-year-old boy with photosensitivity since 3 years of age presented with small concavities on both cheeks, the nasal root and the dorsal surface of both hands. According to the clinical features, erythropoietic protoporphyria (EPP) was suspected. Urine and blood samples were tested for porphyrin derivatives, which revealed a markedly elevated level of erythrocyte protoporphyrin (EP) and a diagnosis of EPP was made. Read More